J Breast Cancer.  2010 Dec;13(4):375-381. 10.4048/jbc.2010.13.4.375.

Hormonal Changes during Extended Letrozole Treatment after Completion of 5 Years of Tamoxifen in Premenopausal Patients with Breast Cancer who Became Postmenopausal

• Cho JY
• Kim HJ
• Lee JW
• Yu JH
• Koh BS
• Yi OV
• Son BH
• Ahn SH

• KMID: 2286525
• DOI: http://doi.org/10.4048/jbc.2010.13.4.375

Abstract

PURPOSE
Extended treatment with aromatase inhibitors (AIs) after tamoxifen has shown effectiveness in postmenopausal patients with breast cancer. However it is very difficult to start on AIs for patients who become postmenopausal after tamoxifen because tamoxifen is a selective estrogen receptor modulator (SERM) that influences menopause, confusing the menopausal status of patients. We assessed the menopausal status and hormone concentrations at the start of letrozole treatment in women with breast cancer who were premenopausal when diagnosed with breast cancer and who became postmenopausal during 5 years of tamoxifen therapy.
METHODS
We evaluated 164 patients with breast cancer who received extended letrozole therapy between May 2006 and December 2007. All had been premenopausal at diagnosis but became postmenopausal during 5 years of tamoxifen therapy. Menopause was defined as amenorrhea for >1 year, serum follicle stimulating hormone (FSH) concentration > or =30 mIU/mL or serum estradiol (E2) concentrations < or =20 pg/mL. FSH and E2 concentrations were monitored for 2 years after starting letrozole therapy.
RESULTS
The median ages of the 164 patients were 45 years at surgery, 46 years when they became amenorrheic, and 50 years at the start of letrozole treatment. Of the 164 patients, 157 (95.7%) were amenorrheic, 14 (9.3%) had FSH concentrations > or =30 mIU/mL and 113 (70.2%) had E2 concentrations < or =20 pg/mL at the start of letrozole. FSH concentrations > or =30 mIU/mL were observed in 87 patients (57.6%) after 6 months of letrozole and in 133 (88.1%) after 2 years, and E2 concentrations < or =20 pg/mL were observed in 164 patients (100%) after 2 years. Times to reach FSH > or =30 mIU/mL and E2 levels < or =20 pg/mL were not significantly related to age at surgery (p=0.836 and p=0.228, respectively), at start of letrozole (p=0.855 and p=0.357, respectively), or at amenorrhea (p=0.098 and p=0.154, respectively).
CONCLUSION
Applying postmenopausal ranges of hormone concentrations observed in normal healthy people to patients who completed 5 years of tamoxifen is inappropriate, because tamoxifen itself may affect FSH concentration. Further studies should focus on identifying an indicator of ovarian function so that these patients can start extended hormone therapy.

Keyword

Aromatase inhibitors; Breast neoplasms; Estradiol; Follicle stimulating hormone

MeSH Terms

Amenorrhea
Aromatase Inhibitors
Breast
Breast Neoplasms
Estradiol
Female
Follicle Stimulating Hormone
Humans
Menopause
Nitriles
Selective Estrogen Receptor Modulators
Tamoxifen
Triazoles
Aromatase Inhibitors
Estradiol
Follicle Stimulating Hormone
Nitriles
Selective Estrogen Receptor Modulators
Tamoxifen
Triazoles

Figure

• 

  Figure 1 Proportion of the patients for each elements of postmenopausal definition, upon start of letrozole therapy. Among the 164 patients, 157 were amenorrheic (95.7%), 14 (9.3%) had FSH concentrations ≥30 mIU/mL and 113 (70.2%) had E2 concentrations ≤20 pg/mL at the start of letrozole treatment, only 10 patients satisfied all 3 elements of postmenopausal defifnition upon start of letrozole therapy. FSH=follicle stimulating hormone; E2=estradiol.

• 

  Figure 2 Proportion of patients with FSH concentrations ≥30 mIU/mL, assessed at 6-month intervals FSH concentrations ≥30 mIU/mL were observed in 14 of 151 patients (9.3%) at the start of letrozole, 87 of 151 patients (57.6%) after 6 month of letrozole and in 133 of 151 (88.1%) after 2 yr. At 2 yr, 18 patients (11.9%) still had low (<30 mIU/mL) serum FSH concentrations. FSH=follicle stimulating hormone.

• 

  Figure 3 Proportions of the patients with E2 concentration <20 pg/mL, assessed at 6-month intervals E2 concentrations ≤20 pg/ mL, observed in 113 patients (70.2%) at the start of letrozole therapy, 145 patietns (90.1%) after 6 month of letrozole and in all 164 patients (100%) after 2 yr. E2=estradiol.

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